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The ratio of high-sensitivity C-reactive protein (hs-CRP) to Serum albumin (SA) (hs-CRP/SA) is emerging as a new potential biomarker capable of stratifying cardiovascular risk in patients with chronic HF (CHF), particularly the risk of major adverse cardiovascular events (MACEs). Objectives: The aim of this study was to evaluate the long-term prognostic value of the hs-CRP/SA ratio on the risk of MACEs in a population of outpatients with CHF. Methods: In this retrospective observational study, 500 patients were enrolled and were stratified into two groups based on the median value of the hs-CRP/SA ratio: 249 patients with hs-CRP/SA < 1.19 and 251 patients with hs-CRP/SA ≥ 1.19. Results: During median follow-up of 5.2 years, 3.6 MACEs/100 patients/year were detected; patients with hs-CRP/SA ≥ 1.19 had a MACE incidence of 5.9 events per 100 patient-years, compared with 1.2 events per 100 patient-years in those with hs-CRP/AS < 1.19 (p < 0.001). Multivariate analysis confirmed that hs-CRP/SA ≥ 1.19 was associated with an approximately 6.5-fold increased risk of new MACEs (HR 6.513, 95% CI 3.928-10.797; p < 0.001). Conclusions: The hs-CRP/SA ratio is confirmed as a powerful prognostic marker in patients with CHF, associated with a significantly increased risk of MACEs.